Ileana L. Piña, MD, MPH; Stefan D. Anker, MD, PhD

Disclosures

May 12, 2015

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Ileana L. Piña, MD, MPH: Hello. I'm Ileana Piña from Montefiore Medical Center and the Albert Einstein Medical School in the Bronx, New York. I am thrilled to be here at the American College of Cardiology in San Diego for our national meeting. The place is bustling with excitement—a lot of interesting and new clinical trials presented in late-breakers that may actually change the way that we practice, both in coronary disease and intervention and in heart failure.

I usually take these opportunities to grab some of my friends who are doing great work in different areas and have them talk to you about it. We hear so much about risk factors for coronary disease, and risk factors for heart failure—and living in the Bronx, we have a high prevalence of obesity. We keep hearing that obesity is associated with hypertension, hyperlipidemia, and glucose intolerance, but we rarely hear the word "cachexia."

I have invited my good friend Dr Stefan Anker, who is professor of medicine and cardiology at the university hospital in Göttingen, Germany, and whom I have known for quite a few years through his work on cachexia, to join me today. There's even a society dedicated to the research of cachexia.

We think about heart failure patients, and many, many years ago, the New England Journal of Medicine had a paper called "The Pathogenesis of Cardiac Cachexia."[1] It has been equated to the concentration camp-looking patient, where they are wasted. But if you come to my heart failure clinic, the majority of patients don't necessarily look like that.

Stefan, I want to welcome you. Tell us a little bit about the society and the work that you have been doing, and tell our audience what "cachexia" really means.

Stefan D. Anker, MD, PhD: Thank you so much for having me. This is an important subject, very close to my heart and unfortunately not studied enough in the world and not given enough attention.

There is a wide spectrum of body weights in our patients, and it can range from the very low, cachectic, muscle-wasted, sarcopenic state to the very obese. We have a good idea of when obesity starts: Overweight starts at a body mass index of 25 kg/m2 and obesity at 30 kg/m2, and of course the real problems occur when you reach body mass indexes of 35 and 40 kg/m2.

Cachexia, coming from kakos and hexis in Greek, means "bad condition." Those patients, they are on the low spectrum, and these are the patients who really have the bad outcomes.

Defining Cachexia

Dr Piña: How do you define it? Is it muscle-mass wasting?

Dr Anker: There are two ways of doing it, and they focus around body weight and body mass index.

If you have a very low body mass index—let's say below 18.5 kg/m2—according the World Health Organization (WHO) criteria, then you can be considered cachectic in any chronic illness. Cachexia also being associated with weight loss can be diagnosed much earlier when you have, let's say, a body mass index below 22 kg/m2 and at least a certain degree of weight loss that is disease-associated. Now, that degree of weight loss can be mild (5%-6%) or more severe (8%-10%). And if you have weight loss of, say, 6% and a body mass index of less than 22 kg/m2, you should be considered cachectic.

Measuring Weight Loss in Heart Failure Patients

Dr Piña: This becomes difficult in heart failure patients, where we look at body weight as volume and we have the patients weighing themselves every day and adding and taking their diuretics. How could I make that assessment in a heart failure patient? Do I look at lean muscle mass? Do I measure it? How do I do that?

Dr Anker: Body composition measurements would be nice to have, but I believe it is too early and too much to ask for this for all heart failure patients. Keeping it simple and focusing first of all on the dry weight will help you a great deal.

Dr Piña: The dry weight at home?

Dr Anker: Yes, the dry weight at home.

Dr Piña: Weighed by their own scale?

Dr Anker: Yes—with their own scale and always at the same time of the day, and under the same general conditions.

Dr Piña: That is so important.

Dr Anker: Ideally, patients should weigh themselves in the morning with their shoes off and after the first passing of urine, and then repeat in a standardized way. If the patients are not edematous at the time, you can accept that weight. And remember, if you discover weight loss despite the patient having some moderate amount of edema, that means that the weight loss is probably even greater.

Dr Piña: We learned many years ago when I was at Temple University and we had probably 30 patients waiting for heart transplants, and we were trying to estimate their dry weight so that we could dose diuretics while they were waiting for their hearts. Very often, we thought we had them at their dry weight, but they were symptomatic, and then we would do right-heart catheterization and their pressures were through the roof. Their dry weight was no longer their dry weight; they had actually lost weight while they were in the hospital.

And of course, muscle mass is an issue. For the practicing clinicians out there, is this a heart failure-generated muscle loss?

Dr Anker: It is loss of muscle, fat tissue, and bone tissue affecting all body compartments that is triggered by the chronic illness. We have found in the past 15 years that there are some common pathways in all chronic illness, including heart failure, chronic obstructive pulmonary disease (COPD), kidney disease, or even cancer, that are very similar across all these diseases that cause the weight loss and affect all body compartments.

Dr Piña: Is it cytokine-related?

Dr Anker: That is part of it—inflammation. But really, neuroendocrine activation can do it. If you have angiotensin and if you have catecholamines, they trigger cell apoptosis and increased energy expenditure—they trigger that in the end, a state of weight loss is promoted.

Diet: "Let Them Eat"

Dr Piña: So, it is a catabolic state, basically.

What about diet? I know that some of the patients lose their taste for food. Maybe it's the sodium restriction; I am trying to get them to not eat as much sodium, and I am trying to get them to watch their caloric intake. Is there a diet that we could specify to the heart failure patients?

Dr Anker: The best thing to avoid cachexia is maybe not to specify a diet, and if they have a good appetite, let them eat.

Dr Piña: Let them eat.

Dr Anker: And let them be essentially happy. Think of quality of life in the very elderly. What do they do? They have some limited family life, some limited interaction with the community, with friends. Take away the appetite, and you take away half the reasons to meet other people.

Dr Piña: That's right, because they share a meal to be social.

Dr Anker: And if you have a dinner invitation but you know that you don't have an appetite, more often than not you will decline the dinner invitation because it is considered impolite by many if you don't eat. Therefore, a good appetite is a good sign for any heart failure patient—and not interfering with this too much is, from a cachexia standpoint at least, a starting point for good preventive medicine.

Appetite Stimulants

Dr Piña: Can I give them an appetite stimulant? Does that work as well?

Dr Anker: The problem, of course, is that these have not been tested in heart failure patients. In principle, they are available, and you have appetite stimulants; Megace® (megestrol acetate) is available in the United States, but of course, it is not indicated for heart failure patients. It is really more in the context of severe anorexia—let's say, for instance, in age-related wasting or in cancer.

Dr Piña: Cancer, I think, is the most common [context in which megestrol acetate is] used.

Dr Anker: Megace is a progesterone derivate, so you will gain weight. The average that you will gain in a few weeks is about 5 kg, but two thirds of that will be fat tissue, which you can consider as a good or bad news—one third will be muscle tissue, but one third is still more than 1.5 kg in such a period.

Whether that translates into improved performance or improved outcome is really a question. So at this stage, I would say appetite stimulation cannot be recommended for heart failure patients. We are lacking the data.

Clinical Trials

Dr Piña: Are we going to do a study with appetite stimulants?

Dr Anker: I wish that it were that easy. The most likely candidates for studies in this field will be skeletal-muscle anabolics or possibly antifatigue drugs, or intravenous iron, because there is lots of iron deficiency also in patients with cachexia.

Dr Piña: And the National Institutes of Health (NIH) has a couple of small trials in the works using intravenous (IV) iron or higher doses of iron.

How many calories should I be recommending to my patients in a day? And what's the balance of protein? I want them to have protein because their muscles are going to need it, and their muscles have wasted from sitting around doing nothing even without the disease.

Dr Anker: This type of research has been done in very few cases. We have published one randomized study[2] on 600-kcal additional nutrition; in order to avoid having too much volume, it was relatively fat-rich, to get the calories in with as little volume as possible. So it is a fine balance.

However, this is opinion-based and level C evidence. We are lacking proper nutritional studies, but for heart failure patients, aim for 2000 or more calories to avoid weight loss or even to promote regaining some of the weight. But one of the best stimulants for appetite is actually encouraging exercise and sport, because that will also promote appetite.

Dr Piña: As you know, in the United States now, cardiac rehabilitation is being covered by Medicare; over 60% of insurers cover it.

Medicare asked us a question not long ago: Where are the billing statements for rehab? We approved it, but people aren't ordering it. And so, this is the other part of heart failure care that really needs that team approach, at least in the clinician line.

Dr Anker: Yes; we are all inherently lazy, and I would not necessarily exclude myself from that. People are looking for therapeutic exercise, if you like, and maybe skeletal-muscle anabolic drugs might be used for that in the future.

Of note, 2 or 3 years ago, there were two testosterone treatment trials: one in women[3] with heart failure, one in men[4] with heart failure. Both had positive results for improving exercise capacity. Can we recommend this on a large scale? Not yet, but this is very encouraging, because it was done also in combination with exercise training programs, and it is very encouraging for future trials.

Dr Piña: Sounds like a good topic for an NIH-type investigator-driven trial.

I want to thank you for coming today. I think this is a topic that we don't pay enough attention to. And my patients in the hospital, especially with hospital food, have very poor appetites. I always try to give them a supplement, but I am worried about the fluid that they are getting with the supplements.

Maybe we give them puddings, or maybe candy bars, and then we call the nutritionist in. I do not think we have paid enough attention to this, and this is why I wanted you to come and talk to us about it.

ESC-HF 2015

Dr Piña: Thank you, and I hope you have a wonderful time here. I want to give you a chance to talk about European Society of Cardiology heart failure meeting coming up in Sevilla.

Dr Anker: Thank you for doing that. That is very close to my heart, having recently been the president of the society. In Sevilla, we have our annual meeting of the Heart Failure Association of the European Society of Cardiology.

We expect almost 5000 people to come. We already have a record numbers of abstract submissions and symposia, and Sevilla is, I very much hope for everybody, a fun place to be. The food will be great, and the weather promises to be possibly even hotter than here in San Diego.

Dr Piña: Yes, it is. And it is the home of flamenco music.

Dr Anker: It's from May 23-26, and you will see not only the best of Europe but also the best of America, because we are reaching out to many of our good friends from the United States, and they are presenting there. This should be a truly international heart failure meeting.

Dr Piña: I hope to be there, and I hope that others get into your website and take a look at your patient education booklets and information, which are terrific.

Dr Anker: You can access the website at heartfailurematters.org

Dr Piña: Thank you. I want to thank my audience for joining me today, and I hope that some of these clinical points make you look at your patients a little bit differently. Take a look at their muscle mass, and refer them to cardiac rehab. It is really highly beneficial, and maybe that combination of appropriate nutrition and exercise will help your patients live longer, stay out of the hospital, and certainly have a better quality of life.

This is Ileana Piña, signing off. Thank you for joining me today.

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